JAK Inhibitor Dose TAPering Strategy Study (JAK-TAP)

August 4, 2026 updated by: University Hospital, Toulouse

JAK Inhibitor Dose TAPering Strategy Study in Low Disease Activity Rheumatoid Arthritis Patients

This study aims to assess the feasibility of tapering JAK inhibitors in rheumatoid arthritis patients in low disease activity by comparing a group of patients tapering the JAK inhibitor dosage to a group of patients continuing the full-dose.

Participants will:

  • Either take

    1. JAK inhibitor dose-tapering strategy.
    2. JAK inhibitor continuous therapy strategy.
  • Visit the clinic once every 3 months for checkups and tests
  • Keep a diary of their treatment intake and symptoms

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Rheumatoid arthritis (RA) is an autoimmune disease leading to inflammation of the synovium and joint erosions, responsible for joint damage leading to pain, functional impairment, work loss and disability. The prognosis of the disease has been greatly improved for 20 years with the use of Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and especially biologic DMARDs.

It is recommended to target remission when initiating a DMARD and to assess patients according to a treat-to-target approach in order to adapt therapy. Once sustained remission is achieved, a decrease in the targeted therapeutic DMARD dose should be considered, according to the recommendations, in order to reduce the risk of adverse events and medical costs. Indeed, targeted DMARDs have considerably increased medical costs linked to RA and studies assessing medical economic impact of bDMARD down-titration on medical costs highlighted the cost-utility of such strategies.

JAK inhibitors, a novel class of targeted therapies have proved to be very effective in treating inflammation and preventing structural progression in RA. However, awareness has recently been raised regarding the safety of JAK inhibitor in the treatment of RA, with particular emphasis on tofacitinib. Indeed, tofacitinib seems to increase the risk of thromboembolism events, infections, neoplasia and major cardiovascular events in comparison to anti-TNF in RA, with a dose-effect.

To date, we have very little data regarding the feasibility of a JAK inhibitor dose-tapering strategy. As a dose-related effect was apparent in terms of major adverse events, we assume that JAK inhibitor dose-tapering strategy might reduce the risk of serious adverse events, without increasing the risk of major flares and thus be beneficial for the patient.

The aim of the study will be to compare a dose-tapering strategy versus therapy continuation in rheumatoid arthritis patients in low disease activity treated with JAK inhibitors on the risk of losing low disease activity despite rescue therapy at 12 months.

1) The dose-tapering strategy will depend on the JAK inhibitor taken by the patient. It will be based on a 50% dose-reduction every 6 months and will comprise 2 steps:

A. Treatment with baricitinib 4 mg daily:

  • Step 1 (after randomization): baricitinib 2mg daily.
  • Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): baricitinib 2mg every other day.

B. Treatment with filgotinib 200 mg daily:

  • Step 1 (after randomisation): filgotinib 100 mg daily.
  • Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): filgotinib 100mg every other day.

C. Treatment with tofacitinib 5 mg twice daily or tofacitinib 11mg daily:

  • Step 1 (after randomisation): tofacitinib 5 mg once daily.
  • Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): tofacitinib 5 mg every other day.

D. Treatment with upadacitinib 15 mg daily:

  • Step 1 (after randomisation): upadacitinib 15 mg every other day.
  • Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): upadacitinib 15 mg every 4 days.

Management of flares:

  1. In case of flare, diagnosed during a scheduled visit: the management of the flare will be standardized by a rescue therapy including a glucocorticoid course and returning to the previous step of JAK inhibitor dose. If the flare is not resolved after the rescue therapy, the patient will be considered in failure of the strategy.
  2. In case of flare between two scheduled visits, an additional visit will be scheduled by the clinical center to confirm the flare by the physician. If the flare is confirmed, the patient will have the standardized flare management as described above.

2) Patients randomised to the control group will have to continue the JAK inhibitor at full dose until the end of the protocol:

  • In case of baricitinib: baricitinib 4mg/day.
  • In case of filgotinib: filgotinib 200mg/day.
  • In case of tofacitinib: tofacitinib 5mg twice daily or 11mg/day.
  • In case of upadacitinib: upadacitinib 15mg/day.

Management of flares:

  1. In case of flare, diagnosed during a scheduled visit: the management of the flare will be standardized by a rescue therapy with a glucocorticoid course. If the flare is not resolved after the rescue therapy, the patient will be considered in failure of the strategy.
  2. In case of flare between two scheduled visits, an additional visit will be scheduled by the clinical center to confirm the flare by the physician. If the flare is confirmed, the patient will have the standardized flare management as described above.

Patients with co-medication with sDMARD or glucocorticoids < 5mg/d will have to keep a stable dose of their treatment during the 12 months of the study in both groups.

Study Type

Interventional

Enrollment (Estimated)

308

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

The inclusion criteria will be

  1. Aged ≥ 18 years at baseline.
  2. Rheumatoid arthritis defined by the ACR/EULAR criteria.
  3. Treated with a JAK inhibitor, full dose for at least 6 months.
  4. The JAK inhibitor is prescribed as monotherapy or combined with a csDMARD with a stable dosage for at least 3 months before inclusion.
  5. Being in LDA (CDAI≤10) for at least 6 months.
  6. With a CRP level below the laboratory standard within the month before the inclusion visit.
  7. Women of childbearing potential (WCBP) must have a negative pregnancy test before starting study

The non-inclusion criteria will be:

  1. Concomitant disease needing to be treated by the JAK inhibitor at full-dose (for example inflammatory bowel disease).
  2. Patient with a history of JAK-inhibitor dose reduction/spacing before enrollment in the study with the JAK-inhibitor currently being taken.
  3. Evidence of flare-up within the last 6 months prior to the inclusion.
  4. Patient who received glucocorticoids > 5mg/day in the 3 months prior the inclusion because of the disease activity of the RA.
  5. Patient requiring corticoid joint injections in the 3 months prior to inclusion or with scheduled joint injections, to control disease activity.
  6. Patient at risk for complication according to the ANSM (60) (current or past smokers, patients at risk of VTE, cancer or major cardiovascular problems, aged ≥ 65 years) at baseline AND currently taking baricitinib or filgotinib.
  7. Patient taking associated bDMARD (including anti-TNF, anti-IL6, anti-CD20, abatacept, anti-IL17, anti-IL12/23, anti-IL23, anti-IL1, anti-BAFF, anti-IL5 pathways).
  8. Patient taking immunotherapy for neoplasia.
  9. Surgery scheduled in the next 12 months.
  10. Fibromyalgia according to the physician's opinion.
  11. Anticipated poor compliance with the strategy.
  12. Patient with any condition that would prevent participation in the study and completion of the study procedures, including language limitation.
  13. Alcohol and/or drug misuse as determined by the investigator.
  14. Pregnancy or breastfeeding.
  15. Non-affiliation to the French Social Security System.
  16. Patient unwilling to sign the informed consent form.
  17. Patient under legal protection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: JAK inhibitor dose-tapering strategy

The dose-tapering strategy will depend on the JAK inhibitor taken by the patient. It will be based on a 50% dose-reduction every 6 months and will comprise 2 steps:

A. Treatment with baricitinib 4 mg daily:

  • Step 1 (after randomization): baricitinib 2mg daily.
  • Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): baricitinib 2mg every other day.

B. Treatment with filgotinib 200 mg daily:

  • Step 1 (after randomisation): filgotinib 100 mg daily.
  • Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): filgotinib 100mg every other day.

C. Treatment with tofacitinib 5 mg twice daily or tofacitinib 11mg daily:

  • Step 1 (after randomisation): tofacitinib 5 mg once daily.
  • Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): tofacitinib 5 mg every other day.

D. Treatment with upadacitinib 15 mg daily:

• Step 1 (after randomisat
Drug: Baricitinib (LY3009104) 4 mg

Treatment with baricitinib 4 mg daily

  • Step 1 (after randomization): baricitinib 2mg daily
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): baricitinib 2mg every other day
Drug: filgotinib 200mg/day

Treatment with filgotinib 200 mg daily

  • Step 1 (after randomisation): filgotinib 100 mg daily
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): filgotinib 100mg every other day
Drug: Tofacitinib 5 mg twice daily

Treatment with tofacitinib 5 mg twice daily or tofacitinib 11mg daily

  • Step 1 (after randomisation): tofacitinib 5 mg once daily
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): tofacitinib 5 mg every other day
Drug: Upadacitinib 15 MG

Treatment with upadacitinib 15 mg daily

  • Step 1 (after randomisation): upadacitinib 15 mg every other day
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): upadacitinib 15 mg every 4 days
Drug: Baricitinib (LY3009104) 4 mg
use of JAK inhibitor at full dose until the end of the protocol
Drug: filgotinib 200mg/day
use of JAK inhibitor at full dose until the end of the protocol
Drug: Tofacitinib 5 mg twice daily
use of JAK inhibitor at full dose until the end of the protocol
Drug: Upadacitinib 15 MG
use of JAK inhibitor at full dose until the end of the protocol
Active Comparator: JAK inhibitor continuous therapy strategy

Full dose will be considered in patient taking:

  • Baricitinib 4mg/day
  • Filgotinib: 200mg/day
  • Tofacitinib : 5mg twice daily or 11mg/day
  • Upadacitinib: 15mg/day
Drug: Baricitinib (LY3009104) 4 mg

Treatment with baricitinib 4 mg daily

  • Step 1 (after randomization): baricitinib 2mg daily
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): baricitinib 2mg every other day
Drug: filgotinib 200mg/day

Treatment with filgotinib 200 mg daily

  • Step 1 (after randomisation): filgotinib 100 mg daily
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): filgotinib 100mg every other day
Drug: Tofacitinib 5 mg twice daily

Treatment with tofacitinib 5 mg twice daily or tofacitinib 11mg daily

  • Step 1 (after randomisation): tofacitinib 5 mg once daily
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): tofacitinib 5 mg every other day
Drug: Upadacitinib 15 MG

Treatment with upadacitinib 15 mg daily

  • Step 1 (after randomisation): upadacitinib 15 mg every other day
  • Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): upadacitinib 15 mg every 4 days
Drug: Baricitinib (LY3009104) 4 mg
use of JAK inhibitor at full dose until the end of the protocol
Drug: filgotinib 200mg/day
use of JAK inhibitor at full dose until the end of the protocol
Drug: Tofacitinib 5 mg twice daily
use of JAK inhibitor at full dose until the end of the protocol
Drug: Upadacitinib 15 MG
use of JAK inhibitor at full dose until the end of the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
proportion of patients still receiving a JAK-inhibitor
Time Frame: 12 post baseline

The primary outcome of this study will be the proportion of patients still receiving a JAK-inhibitor and being in CDAI low disease activity at 12 months.

The size of the effect will be given in the form of the difference in proportion between the two treatment groups with a two-sided confidence interval at 95%. Non-inferiority will be assessed with this interval. Non-inferiority will be concluded if the lower limit of the 95% confidence interval does not exceed the non-inferiority margin of 10% of the difference in proportion.
12 post baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Flare occurence
Time Frame: first flare post baseline

The delay between the inclusion visit and the first flare diagnosed by a physician.

Two definitions of flare can be used for this criterion:

  • A flare defined by a CDAI > 10 at any visit.

  • A major flare at any visit, based on the OMERACT definition which is:

    • An increase in the DAS28-ESR score of more than 1.2 compared to baseline score,
    • OR a DAS28-ESR score increase of more than 0.6 compared to the baseline score AND the current DAS28-ESR score being above 3.2.
first flare post baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Toulouse

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2025

Primary Completion (Estimated)

April 1, 2029

Study Completion (Estimated)

April 1, 2029

Study Registration Dates

First Submitted

October 29, 2024

First Submitted That Met QC Criteria

November 12, 2024

First Posted (Actual)

November 13, 2024

Study Record Updates

Last Update Posted (Actual)

August 7, 2026

Last Update Submitted That Met QC Criteria

August 4, 2026

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/23/0373
  • 2023-509788-25-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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